Low T and Aging
Serum testosterone levels gradually decline as men age, but the degree to which serum testosterone levels decline, as well as the extent of associated clinical changes (reduced libido, low bone mineral density and height loss, and decreased energy), is variable.
This age-related decline in serum testosterone levels has been confirmed in several cross-sectional and longitudinal studies and results from dysfunction in the hypothalamic-pituitary-testicular axis.2-4 The clinical importance of this decline is controversial, however. Recognizing this variability and understanding what may be considered changes in body function due to "normal aging" versus potentially treatable age-related testosterone (or androgen) deficiency is crucial in the care of older men. The role of evaluating testosterone levels and their clinical significance is reviewed here.
Aging is associated with declines in total serum testosterone concentration, increases in sex hormone-binding globulin (SHBG) concentration, and decreases in free testosterone. In one large cross-sectional study of more than 3000 men ages 40 to 79, serum testosterone concentration fell 0.4% per year, free testosterone concentration 1.3%.3 In another study, of 890 men, total testosterone levels were
Free testosterone is considered the biologically active form of the sex hormone-binding globulin (SHBG). As men age, SHBG level rises, binding more testosterone and leaving less free testosterone available to act on target tissues. There is no uniformity in how aging men respond to this changing hormonal milieu, however. As a result, a controversy exists about whether this is a disease state. When it comes to low testosterone, what is normal senescence? What is illness?
Symptoms and signs suggestive of androgen deficiency in older men include reduced libido, low bone mineral density and height loss, and, less specifically, decreased energy, anemia, depressed mood, reduced muscle strength and bulk, and increased body fat.5 When these signs and symptoms accompany significantly lower levels of both types of testosterone, the patient may be diagnosed with late-onset hypogonadism. Cutoffs for the definition of low testosterone vary, although generally accepted values are =200 or =300 ng/dL of total testosterone.6
Unlike younger men with hypogonadism who present prominently with specific gonadal dysfunction (for example, infertility, incomplete or delayed sexual development), older men have nonspecific symptoms that can frequently be caused by other common disorders. For example, in the largest longitudinal study of testosterone deficiency, researchers found that up to 25% of elderly men who complained of sexual dysfunction, including low libido and erectile dysfunction, had normal-range testosterone levels for their age.7 In light of these findings, what is the best approach to patients who may—or may not—need treatment?
The Endocrine Society updated its clinical guidelines on androgen deficiency evaluation and treatment in 2010.6 It proposed a practical approach to evaluating testosterone deficiency in older men who present with low libido, decreased energy, depressed mood, osteoporosis, or recent fracture. If a clinician suspects testosterone deficiency, the first step should include an early morning total testosterone measurement. If the level is
To date, there are relatively few well-designed, large studies on hypogonadism in aging men. To better understand if this is a distinct clinical syndrome, future trials should be powered to assess whether testosterone deficiency in older men independently predicts important outcomes such as osteoporosis, muscle strength, mood disorders, and sexual dysfunction. This will best inform us as we try to move forward with treatment.
- Medpage Today, Sanjai Sinha, MD. Testosterone Decline With Aging: What Is Normal? .
- Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2002;87:589-598.
- Wu FC, Tajar A, Pye SR, et al. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab. 2008;93:2737-2745.
- Harman SM, Metter EJ, Tobin JD, et al; Baltimore Longitudinal Study of Aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001;86:724-731.
- Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010; 95:2536–2559
- Araujo AB, Esche GR, Kupelian V, et al. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab. 2007;92:4241-4247
- Wu FC, Tajar A, Beynon JM, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363:123-135